1. Field of the Invention
The present invention relates generally to bulk density measurements and, more particularly, relates to systems and methods for sampling a bulk material, such as a powder, to measure its density.
2. Description of the Related Art
A process known as spray drying is used to manufacture a number of amorphous drug substances. In a conventional spray drying process, a compound is dissolved in an appropriate solvent and the resulting solution is atomized in a hot inert atmosphere that facilitates evaporation. As the solvent evaporates, the resulting particles drift downward, similar to snow, through a series of chambers and are eventually collected in a container. The container can include what is commonly referred to as an intermediate bulk container, or IBC.
In a variant of this process known as spray dried dispersion, a polymer is added to the solution so that the drug substance is embedded in a polymer matrix upon evaporation of the solvent. During the particles' descent through the series of chambers, their physical characteristics are sampled in various ways to assess their quality. For example, particle size can be measured by light scattering. Such online testing allows the plant operator to monitor the manufacturing in real time, or near real time, and thus ensure that the process is continuously within specification. Offline, batch testing of the same physical parameters does not allow for continuous adjustment of the process, and thus may result in entire batches being discarded because of insufficient quality. Parameters used to ensure the integrity of the manufacturing process are called commonly referred to as “Critical to Quality Attributes,” or CQA.
In addition to particle size, another important CQA for spray drying is bulk density. Conventionally, bulk density is measured by scooping some powder out of the IBC, transferring the powder to a graduated cylinder, then weighing the powder and the cylinder. To obtain an accurate measurement, care must be taken not to cause tamping or settling of the powder. The density thus obtained is representative of the “bulk” material, that is, material that has not significantly settled under its own weight. The density of a solid material can be difficult to measure, depending on how its volume is defined. For example, gently pouring sand into a container will result in a lower density measurement than if the sand was compacted into the same container. The compacted sand will occupy less volume and thus exhibit a higher density. Powders and granular solids such as sand contain pockets of air in between individual grains. The density of the material including the air spaces is the bulk density, which differs significantly from the density of an individual granule or grain of the material with no air included.
The conventional method for measuring bulk density suffers significant drawbacks, however. With reference now to FIG. 1, a typical spray drying configuration includes one or more spray drying chambers 2, a chute 3, and a collection container 4. The chute 3 channels powder from the last spray drying chamber to the container 4. To sample material in a conventional spray drying system, a shutoff valve is closed to stop the flow of material into the container 4. The valve may include, for example, a butterfly valve disposed inside the chute 3 above the collection container 4. The container 4 is then disconnected from the chute 3 and wheeled away. After a second collection container 4 is wheeled into place and connected to the chute 3, the butterfly valve or other shutoff valve is reopened.
To collect a sample, an operator climbs onto a platform, reaches into the now-disconnected collection container 4, and removes material, such as a powder, from several locations to form an aggregate “sample.” This sample is carefully transferred to a graduated cylinder for weighing. The entire process typically takes about fifteen minutes and involves moving heavy equipment. This process of collecting a sample requires a time consuming interruption to the spray drying process. Current methods also require the operator to scoop out some material from several locations in the container 4 to form an aggregate “sample,” which may not be representative of the flow of material at any given moment. The current measurement process is thus cumbersome, time consuming, and imprecise.
Therefore, among other disadvantages, current designs cannot achieve accurate measurements with minimal movement of large, heavy containers and minimal interruption to the spray drying process. Thus, accurate, controlled, reliable, and reproducible bulk density sampling and measurement remains a significant challenge.